The approximate 24% annual gross mortality of US hemodialysis patients is unacceptably high. The precise reason for this variance in mortality may relate to the quantity of dialysis delivered. The definition of adequate dialysis derived from the NCDS is inapplicable to today's older patients with more co-morbidity, and to current dialysis conditions in which dialyzer reuse is prevalent. The conventional methods for calculating the critical variable, the total urea clearance per dialysis normalized for urea's distribution volume (KT/V), may be inadequate in its assumption of a single pool of distribution. The influence of the more costly, but biocompatable, high flux dialyzers is unresolved. Lastly, the impact of rigorous monitoring of dialysis delivery and the practice of standards for general medical care on patient survival, morbidity, rehabilitation, and compliance is unknown. Because of these critical deficiencies in the knowledge for the care of Americans with ESRD, we propose to serve as a "Clinical Center" in cooperative agreement with the MDDK and with other approved Centers in the full-scale phase of the Mortality and Morbidity in Hemodialysis Patients Trial as defined in the "Study Protocol" of 12/23/93. In this prospective, multicenter, randomized, two-by-two factorial trial, we propose that a high delivered KT/V and (or) dialysis with a biocompatable, high flux membrane material will reduce patient mortality and morbidity. The interventions are: (1) the KT/V as calculated by a two pool volume of distribution formulation, and (2) the concurrent dialyzer flux for large molecular weight solutes and its biocompatability. For the KT/V component, the target values of 1.4 (range of 1.3 to 1.5) and 1.0 (0.9 to 1.1) will be calculated by either the Smye method, the Baxter or Fresenius Dialysis Sampler method, or the 30 minute rebound method. The other variable will be the flux capacity and the biocompatability of the dialysis membrane, based upon a functional definitions of the beta2-MG sieving coefficient, and intradialytic neutropenia and complement generation. respectively. The primary outcome will be the patients' death rate, and the secondary outcomes will be the hospitalization rate and frequency for non-access related problems, cardiac disease, and infections, and a decline in the serum albumin concentration. We will be responsible for the timely retrieval of the appropriate blood samples, the administration and retrieval of questionnaires, monitoring the clinical status of the patients and maintaining their health, documenting that the protocol is being strictly adhered to by the patients and the dialysis facilities, replacing patients that die or who drop out of the study, transmitting the appropriate blood and urine samples to the Central Biochemistry Laboratory and the test results and information to the DCC, monitoring local quality control, and participating in all conjoined Center and Committee activities.